Correlation between Chronic Pain with BDNF Levels, Histophatology of Hippocampus, and Spatial Memory in Wistar Rats

Trianggoro Budisulistyo; Widiastuti Samekto; Dwi Pudjonarko; Herlina Suryawati; Suryadi Suryadi; Maria Wahyuni

doi:10.3889/oamjms.2023.10710

Authors

Trianggoro Budisulistyo Department of Neurology, Medical Faculty, Diponegoro University, Dr. Kariadi General Hospital, Semarang, Central Java, Indonesia https://orcid.org/0000-0001-8085-5030
Widiastuti Samekto Department of Neurology, Medical Faculty, Diponegoro University, Dr. Kariadi General Hospital, Semarang, Central Java, Indonesia
Dwi Pudjonarko Department of Neurology, Medical Faculty, Diponegoro University, Dr. Kariadi General Hospital, Semarang, Central Java, Indonesia
Herlina Suryawati Department of Neurology, Medical Faculty, Diponegoro University, Dr. Kariadi General Hospital, Semarang, Central Java, Indonesia
Suryadi Suryadi Department of Neurology, Medical Faculty, Diponegoro University, Dr. Kariadi General Hospital, Semarang, Central Java, Indonesia
Maria Wahyuni Department of Neurology, Medical Faculty, Diponegoro University, Dr. Kariadi General Hospital, Semarang, Central Java, Indonesia https://orcid.org/0000-0002-8467-5771

DOI:

https://doi.org/10.3889/oamjms.2023.10710

Keywords:

Chronic pain, Brain derived neurotrophic factor, Spatial memory, Histopathology of hippocampus, Wistar rats, Periodontitis

Abstract

BACKGROUND: Pain is defined as an unpleasant sensory and emotional experience associated with actural or potential tissue damage. Cognitive impairment can occur due to various processes in the brain, one of which resulted from chronic pain. Brain-derived neurotrophic factor (BDNF) is a neurotropin that plays a role in mediating disinhibition in the excitability of the motor cortex of the brain and inhibitory function in descending pain pathways. Chronic pain of periodontitis causes systemic inflammation that activates microglia resulting in degeneration of CA1 pyramidal neurons in the hippocampus and affects cognitive function, especially spatial memory.

AIM: The objectives of this study were to determine the correlation between BDNF levels, spatial memory, and histopathology of hippocampus on periodontitis Wistar rats.

METHODS: This observational prospective study was conducted between January and April 2022 at Laboratory Negeri Semarang University. Frontal inferior teeth ligation of Wistar rats was carried out to induce periodontitis for 4 weeks. Chronic pain was assessed using Rat Grimace Scale. Morris water maze (MWM) adaptation was applied for 4 weeks and then BDNF levels, spatial memory, and histopathology of hippocampus were investigated. T-test independent and spearman correlation test were used to data analysis.

RESULTS: Among 12 rats, the mean of BDNF levels, spatial memory, and histopathology of hippocampus score were 7.57 ng/mL, 65.08 second, and 3, respectively. There were significant relationships between BDNF levels (p = 0.028), spatial memory (p = 0.001), and histopathology of hippocampus score (p = 0.017) on Wistar rats with chronic pain. Strong correlation (r = −0.721, r²= 0.52, p = 0.004) between BDNF levels and spatial memory, and moderate correlation (r = −0.597, p = 0.02) between BDNF levels and histopathology of hippocampus score was obtained. There was no significant correlation between spatial memory and histopathology of hippocampus score.

CONCLUSIONS: There were significant differences between BDNF levels, spatial memory, and histopathology of hippocampus on periodontitis Wistar rats.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Cohen M, Quintner J, van Rysewyk S. Reconsidering the international association for the study of pain definition of pain. Pain Rep. 2018;3(2):e634. https://doi.org/10.1097/PR9.0000000000000634 PMid:29756084 DOI: https://doi.org/10.1097/PR9.0000000000000634

Taylor JJ. Protein biomarkers of periodontitis in saliva. ISRN Inflamm. 2014;2014:593151. https://doi.org/10.1155/2014/593151 PMid:24944840 DOI: https://doi.org/10.1155/2014/593151

Herrera BS, Martins-Porto R, Maia-Dantas A, Campi P, Spolidorio LC, Costa SK, et al. iNOS-derived nitric oxide stimulates osteoclast activity and alveolar bone loss in ligature-induced periodontitis in rats. J Periodontol. 2011;82(11):1608-15. https://doi.org/10.1902/jop.2011.100768 PMid:21417589 DOI: https://doi.org/10.1902/jop.2011.100768

Marchand S. The physiology of pain mechanisms: From the periphery to the brain. Rheum Dis Clin North Am. 2008;34(2):285-309. https://doi.org/10.1016/j.rdc.2008.04.003 PMid:18638678 DOI: https://doi.org/10.1016/j.rdc.2008.04.003

Miranda M, Morici JF, Zanoni MB, Bekinschtein P. Brain-Derived neurotrophic factor: A key molecule for memory in the healthy and the pathological brain. Front Cell Neurosci. 2019;13:363. https://doi.org/10.3389/fncel.2019.00363 PMid:31440144 DOI: https://doi.org/10.3389/fncel.2019.00363

Lu B, Nagappan G, Lu Y. BDNF and synaptic plasticity, cognitive function, and dysfunction. Handb Exp Pharmacol. 2014;220:223-50. https://doi.org/10.1007/978-3-642-45106-5_9 PMid:24668475 DOI: https://doi.org/10.1007/978-3-642-45106-5_9

Ionel A, Lucaciu O, Moga M, Buhatel D, Ilea A, Tabaran F, et al. Periodontal disease induced in Wistar rats-experimental study. Hum Vet Med. 2015;7(2):90-5.

Lee JH, Lin JD, Fong JI, Ryder MI, Ho SP. The adaptive nature of the bone-periodontal ligament-cementum complex in a ligature-induced periodontitis rat model. Biomed Res Int. 2013;2013:876316. https://doi.org/10.1155/2013/876316 PMid:23936854 DOI: https://doi.org/10.1155/2013/876316

Sotocinal SG, Sorge RE, Zaloum A, Tuttle AH, Martin LJ, Wieskopf JS, et al. The rat grimace scale: A partially automated method for quantifying pain in the laboratory rat via facial expressions. Mol Pain. 2011;7(1):1-10. https://doi.org/10.1186/1744-8069-7-55 PMid:21801409 DOI: https://doi.org/10.1186/1744-8069-7-55

Vorhees CV, Williams MT. Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006;1(2):848-58. https://doi.org/10.1038/nprot.2006.116 PMid:17406317 DOI: https://doi.org/10.1038/nprot.2006.116

Barnhart CD, Yang D, Lein PJ. Using the Morris water maze to assess spatial learning and memory in weanling mice. PLoS One. 2015;10(4):e0124521. https://doi.org/10.1371/journal.pone.0124521 PMid:25886563 DOI: https://doi.org/10.1371/journal.pone.0124521

Arifin WN, Zahiruddin WM. Sample size calculation in animal studies using resource equation approach. Malays J Med Sci. 2017;24(5):101-5. https://doi.org/10.21315/mjms2017.24.5.11 PMid:29386977 DOI: https://doi.org/10.21315/mjms2017.24.5.11

Duric V, McCarson KE. Persistent pain produces stress-like alterations in hippocampal neurogenesis and gene expression. J Pain. 2006;7(8):544-5. https://doi.org/10.1016/j.jpain.2006.01.458 PMid:16885011 DOI: https://doi.org/10.1016/j.jpain.2006.01.458

Stefani LC, Torres IL, de Souza IC, Rozisky JR, Fregni F, Caumo W. BDNF as an effect modifier for gender effects on pain thresholds in healthy subjects. Neurosci Lett. 2012;514(1):62-6. https://doi.org/10.1016/j.neulet.2012.02.057 PMid:22395087 DOI: https://doi.org/10.1016/j.neulet.2012.02.057

Smith PA. BDNF: No gain without pain? Neuroscience. 2014;283:107-23. https://doi.org/10.1016/j.neuroscience.2014.05.044 PMid:24887639 DOI: https://doi.org/10.1016/j.neuroscience.2014.05.044

Saffarpour S, Shaabani M, Naghdi N, Farahmandfar M, Janzadeh A, Nasirinezhad F. In vivo evaluation of the hippocampal glutamate, GABA and the BDNF levels associated with spatial memory performance in a rodent model of neuropathic pain. Physiol Behav. 2017;175:97-103. https://doi.org/10.1016/j.physbeh.2017.03.025 PMid:28336100 DOI: https://doi.org/10.1016/j.physbeh.2017.03.025

Jain A. Mechanisms underlying exercise-induced BDNF stimulated memory improvements in rodents. Undergrad Res Nat and Clin Sci Technol J. 2021;5:1-7. DOI: https://doi.org/10.26685/urncst.298

Zhu W, Yao Y, Hao J, Li W, Zhang F. Short-term postoperative pain and function of unilateral biportal endoscopic discectomy versus percutaneous endoscopic lumbar discectomy for single-segment lumbar disc herniation: A systematic review and meta-analysis. Appl Bionics Biomech. 2022;2022:5360277. https://doi.org/10.1155/2022/5360277 PMid:35465181 DOI: https://doi.org/10.1155/2022/5360277

Ocampo AC, Squire LR, Clark RE. Hippocampal area CA1 and remote memory in rats. Learn Mem. 2017;24(11):563-8. https://doi.org/10.1101/lm.045781.117 PMid:29038217 DOI: https://doi.org/10.1101/lm.045781.117

Bechara RG, Lyne R, Kelly ÁM. BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat. Behav Brain Res. 2014;275:297-306. https://doi.org/10.1016/j.bbr.2013.11.015 PMid:24269499 DOI: https://doi.org/10.1016/j.bbr.2013.11.015

Tyler WJ, Alonso M, Bramham CR, Pozzo-Miller LD. From acquisition to consolidation: On the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem. 2002;9(5):224-37. https://doi.org/10.1101/lm.51202 PMid:12359832 DOI: https://doi.org/10.1101/lm.51202

Clark RE, Broadbent NJ, Squire LR. Hippocampus and remote spatial memory in rats. Hippocampus. 2005;15(2):260-72. https://doi.org/10.1002/hipo.20056 PMid:15523608 DOI: https://doi.org/10.1002/hipo.20056

O’Keefe J, Speakman A. Single unit activity in the rat hippocampus during a spatial memory task. Exp Brain Res. 1987;68:1-27. https://doi.org/10.1007/BF00255230 DOI: https://doi.org/10.1007/BF00255230